Cognitive impairment is commonly reported by smokers attempting to quit. Such symptoms prompt relapse to smoking, perhaps to ameliorate these deficits and restore functioning to pre-cessation levels. Indeed, objectively assessed cognitive impairment increases risk of smoking relapse, supporting the premise that withdrawal-related cognitive impairment is an important therapeutic target to aid in smoking cessation. The proposed randomized clinical trial will evaluate a cognitive remediation training (CRT) intervention to ameliorate abstinence-induced cognitive impairment and improve quitting success in treatment-seeking smokers. Specifically, we will evaluate whether computer-assisted CRT improves quitting success with nicotine patch therapy, the most widely used medication for smoking cessation in the U.S. Three hundred and forty smokers will receive nicotine patch therapy, plus either: (a) computer-assisted CRT or (b) a cognitive stimulation control (CSC) intervention, based on random assignment. The CRT intervention is a 12-week standardized course (36 hours total) of computerized cognitive exercises designed to buffer smokers against cognitive deficits that increase smoking relapse risk. CSC (control condition) is an active intervention designed to address the non-specific effects of attention and computer stimulation. CRT or CSC will be initiated 4 weeks prior to the target quit date. Standard 8-week open-label nicotine patch therapy will commence on the target quit date for participants in both study conditions. The primary outcome will be biochemically verified point-prevalence abstinence at the 6-month follow-up. Secondary outcomes include end of treatment quit rates, time to relapse, and recovery rate from smoking lapses. Key intermediate endpoints include changes in cognitive performance and brain function (primary), as well as craving, functional status, and adherence. To examine pre- to post-treatment changes in brain function associated with CRT vs. CSC, BOLD fMRI data will be acquired for a subset of participants (n=50) pre- and post-treatment while they complete neurocognitive tasks. Thus, in addition to evaluating the efficacy of a novel CRT intervention, this study will provide a critical mechanistic understanding of the role of cognitive function in smoking relapse. PUBLIC HEALTH RELEVANCE: The proposed research focuses on nicotine dependence, one of the most important medical and public health problems. The science is built upon a firm foundation of empirical evidence supporting cognition as a target for nicotine dependence treatment, thus driving the field forward from observational data to clinical intervention. The novel web-based computerized cognitive training intervention is "portable" and can be easily translated to clinical practice for the treatment for nicotine dependence.